Clinicopathologic conference: A three-month-old infant with failure to thrive, hepatomegaly, and neurological impairment

A 3.5-month-old white male was admitted to hospital to be evaluated for liver disease. Birth weight was 3,000 g; occipito-frontal head circumference (OFC) was 36-37 cm. At birth he had a heart murmur, undescended testes, and increased muscle tone. He had a 'trigonocephalic' skull with a flat top, prominent occiput, with bridging of the lambdoid and posterior sagittal sutures. The anterior fontanelle measured 3 x 3 cm. He had decreased range of motion of shoulders, 20° flexion contracture of the elbows, and bilateral cryptorchidism. During hospitalization he failed to gain weight on adequate caloric intake and he developed hepatomegaly. An intravenous pyelogram suggested presence of a horseshoe kidney. The boy's intrauterine growth had been normal; postnatal growth was severely impaired. The infant was hypertonic, lacked the typical Zellweger syndrome appearance and epiphyseal cartilage stippling; several EEG's were normal. The fundi were peripherally hypopigmented in a manner suggesting retinitis pigmentosa, and there was hypochromic anemia. However, the infant did have increased serum iron, saturated iron binding capacity and transferrin levels. The infant lived longer than most Zellweger syndrome patients do, dying suddenly at 15 months. Profound psychomotor retardation, apparent blindness and deafness, and liver disease were present before death. The clinical picture was sufficiently atypical so that the authors spoke of a 'metabolic disorder similar to Zellweger syndrome ...', but autopsy findings were exactly like those in classic Zellweger syndrome. The patient apparently had the hypertonic 'Zellweger syndrome-like' disorder reported by Versmold et al. One of the co-authors of the Versmold et al. paper (prof. H.J. Bremer, Dusseldorf) wrote to the author of this article on 11 March, 1976 that he examined 2 additional children, both with the 'classic' [Zellweger syndrome] manifestations. In these children he also found the defect of particulate catalase (no defect of the non-particulate catalase of cells such as erythrocytes) and the same redox changes of cytochrome b and c as in the clinically somewhat atypical case.